Aqueous pharmaceutical compositions including eye drops and the like are required to have sufficient preservatives-effectiveness in order to prevent them from being contaminated by microorganisms during production or use of the compositions. The preservatives-effectiveness is usually checked by the preservatives-effectiveness tests prescribed in the general information of the Japanese Pharmacopoeia.
To impart sufficient preservatives-effectiveness to the aqueous pharmaceutical composition, it has been considered essential to contain the preservatives, in particular, benzethonium chloride, benzalkonium chloride, parabens, chlorobutanol, sorbic acid or their salts, or the like. However, there is a concern that use of some kinds of preservatives may have an adverse effect on some tissues, for example, the cornea or the like. Therefore, it is desirable that aqueous pharmaceutical compositions doesn't contain any kinds of preservatives, or contain them in lower concentration if we have to add some preservatives.
The absence of preservative naturally suggests that the composition will not pass the preservatives-effectiveness tests. There is proposed another method where no preservative is added, i.e., a method of using as containers for holding aqueous pharmaceutical compositions therein a special container, notably, a filter-equipped container or a disposable container (single-unit container). The filter-equipped container can prevent the entry of bacteria into the contents, i.e., constitutionally prevent the contamination of the contents (JP 2004-051170 A and JP 2004-166978 A). The disposable container is discarded once opened and used, so that the polluted container will not be used again even if bacteria are mixed into the contents of the container. The method of using such a filter-equipped container or disposable container is considered remarkably advantageous as the method where no preservative is added to the aqueous pharmaceutical compositions.
However, use of the disposable container will lead to loss of much liquid medication. For convenience in dividing the medication into portions, it is necessary to pack the liquid medication in each container with excess of the single quantity to be used at one time. This is highly disadvantageous, especially for the medication containing expensive raw materials. In addition, some disposable containers are in special shapes or others have to be treated differently from general containers, for example, by discarding the first one drop of medication prior to the use. This may cause various problems in use. In contrast to this, the filter-equipped container has the advantage of being treated in the same manner as in the general containers. This means the users can treat the filter-equipped container without recognizing the filter-equipped container as a special one, which can significantly reduce unexpected troubles.
As previously mentioned, it is considered extremely useful to fill a filter-equipped container with an aqueous pharmaceutical composition free of preservative that may have an adverse effect on some tissues, such as the cornea or the like.
In light of the structure of the container, the aqueous pharmaceutical composition is allowed to pass through the filter installed in the container. Therefore, consideration should be given to the interaction between the ingredients contained in the aqueous pharmaceutical composition and the filter installed in the container. There are some materials that tend to be easily adsorbed by the filter due to their chemical or physical properties. In other words, the compatibility between the aqueous pharmaceutical composition and the material for constituting the filter is important when the aqueous pharmaceutical composition is filled in the filter-equipped container.